Dilini Pinnaduwage

Investigating the clinical advantages of a robotic linac equipped with a multileaf collimator in the treatment of brain and prostate cancer patients

The purpose of this study was to evaluate the performance of a commercially available CyberKnife system with a multileaf collimator (CK‐MLC) for stereotactic body radiotherapy (SBRT) and standard fractionated intensity‐modulated radiotherapy (IMRT) applications. Ten prostate and ten intracranial cases were planned for the CK‐MLC. Half of these cases were compared with clinically approved SBRT plans generated for the CyberKnife with circular collimators, and the other half were compared with clinically approved standard fractionated IMRT plans generated for conventional linacs. The plans were compared on target coverage, conformity, homogeneity, dose to organs at risk (OAR), low dose to the surrounding tissue, total monitor units (MU), and treatment time. CK‐MLC plans generated for the SBRT cases achieved more homogeneous dose to the target than the CK plans with the circular collimators, for equivalent coverage, conformity, and dose to OARs. Total monitor units were reduced by 40% to 70% and treatment time was reduced by half. The CK‐MLC plans generated for the standard fractionated cases achieved prescription isodose lines between 86% and 93%, which was 2%–3% below the plans generated for conventional linacs. Compared to standard IMRT plans, the total MU were up to three times greater for the prostate (whole pelvis) plans and up to 1.4 times greater for the intracranial plans. Average treatment time was 25 min for the whole pelvis plans and 19 min for the intracranial cases. The CK‐MLC system provides significant improvements in treatment time and target homogeneity compared to the CK system with circular collimators, while maintaining high conformity and dose sparing to critical organs. Standard fractionated plans for large target volumes (>100 cm3) were generated that achieved high prescription isodose levels. The CK‐MLC system provides more efficient SRS and SBRT treatments and, in select clinical cases, might be a potential alternative for standard fractionated treatments. PACS numbers: 87.56.nk, 87.56.bd

Improving plan quality and consistency by standardization of dose constraints in prostate cancer patients treated with CyberKnife.

Treatment plans for prostate cancer patients undergoing stereotactic body radiation therapy (SBRT) are often challenging due to the proximity of organs at risk. Today, there are no objective criteria to determine whether an optimal treatment plan has been achieved, and physicians rely on their personal experience to evaluate the plans quality. In this study, we propose a method for determining rectal and bladder dose constraints achievable for a given patients anatomy. We expect that this method will improve the overall plan quality and consistency, and facilitate comparison of clinical outcomes across different institutions. The 3D proximity of the organs at risk to the target is quantified by means of the expansion‐intersection volume (EIV), which is defined as the intersection volume between the target and the organ at risk expanded by 5 mm. We determine a relationship between EIV and relevant dosimetric parameters, such as the volume of bladder and rectum receiving 75% of the prescription dose (V75%). This relationship can be used to establish institution‐specific criteria to guide the treatment planning and evaluation process. A database of 25 prostate patients treated with CyberKnife SBRT is used to validate this approach. There is a linear correlation between EIV and V75% of bladder and rectum, confirming that the dose delivered to rectum and bladder increases with increasing extension and proximity of these organs to the target. This information can be used during the planning stage to facilitate the plan optimization process, and to standardize plan quality and consistency. We have developed a method for determining customized dose constraints for prostate patients treated with robotic SBRT. Although the results are technology‐specific and based on the experience of a single institution, we expect that the application of this method by other institutions will result in improved standardization of clinical practice. PACS numbers: 87.55.‐x, 87.55.D‐, 87.55.de, 87.55.dk

Comparison between target margins derived from 4DCT scans and real‐time tumor motion tracking: Insights from lung tumor patients treated with robotic radiosurgery

PURPOSE A unique capability of the CyberKnife system is dynamic target tracking. However, not all patients are eligible for this approach. Rather, their tumors are tracked statically using the vertebral column for alignment. When using static tracking, the internal target volume (ITV) is delineated on the four-dimensional (4D) CT scan and an additional margin is added to account for setup uncertainty [planning target volume (PTV)]. Treatment margins are difficult to estimate due to unpredictable variations in tumor motion and respiratory pattern during the course of treatment. The inability to track the target and detect changes in respiratory characteristics might result in geographic misses and local tumor recurrences. The purpose of this study is to develop a method to evaluate the adequacy of ITV-to-PTV margins for patients treated in this manner. METHODS Data from 24 patients with lesions in the upper lobe (n = 12), middle lobe (n = 3), and lower lobe (n = 9) were included in this study. Each patient was treated with dynamic tracking and underwent 4DCT scanning at the time of simulation. Data including the 3D coordinates of the target over the course of treatment were extracted from the treatment log files and used to determine actual target motion in the superior-inferior (S-I), anterior-posterior (A-P), and left-right (L-R) directions. Different approaches were used to calculate anisotropic and isotropic margins, assuming that the tumor moves as a rigid body. Anisotropic margins were calculated by separating target motion in the three anatomical directions, and a uniform margin was calculated by shifting the gross tumor volume contours in the 3D space and by computing the percentage of overlap with the PTV. The analysis was validated by means of a theoretical formulation. RESULTS The three methods provided consistent results. A uniform margin of 4.5 mm around the ITV was necessary to assure 95% target coverage for 95% of the fractions included in the analysis. In the case of anisotropic margins, the expansion required in the S-I direction was larger (8.1 mm) than those in the L-R (4.9 mm) and A-P (4.5 mm) directions. This margin accounts for variations of target position within the same treatment fraction. CONCLUSIONS The use of bony alignment for CyberKnife lung stereotactic body radiation therapy requires careful considerations, in terms of the potential for increased toxicity or local miss. Our method could be used by other centers to determine the adequacy of ITV-to-PTV margins for their patients.

Whole-Procedural Radiological Accuracy for Delivering Multi-Session Gamma Knife Radiosurgery with a Relocatable Frame System

A newly developed Gamma Knife relocatable eXtend frame system has enabled the delivery of multi-session Gamma Knife radiosurgery without the use of skull pin fixation frame system. In this study, we investigate and report for the first time the whole procedural radiological accuracy for administering such treatments. To quantify the radiological alignment, the commonly used Winston-Lutz test was modified and used to determine the device accuracy of the eXtend frame system. Patient setup uncertainties relative to the device were further measured for a series of treatment sessions (n = 58), and then incorporated with the Winston-Lutz test results from individual patient-specific eXtend frame systems. The whole-procedure mean 3D radiological setup uncertainty was determined to be 0.69 ± 0.73 mm (1σ) from all the cases analyzed, and the mean 90% confidence level margins were found to be 0.55, 0.78 and 0.72 mm along the x-, y-, and z-axis, respectively. Our results therefore demonstrated that sub-millimetric radiological accuracy is clinically achievable for multi-session Gamma Knife radiosurgery treatments and a 1 mm margin along the major axes is sufficient for planning multi-session Gamma Knife radiosurgery treatments.

Analysis of Dose Distribution and Risk of Pneumonitis in Stereotactic Body Radiation Therapy for Centrally Located Lung Tumors A Comparison of Robotic Radiosurgery, Helical Tomotherapy and Volumetric Modulated Arc Therapy

Stereotactic body radiation therapy (SBRT) to central lung tumors is associated with normal -tissue toxicity. Highly conformal technologies may reduce the risk of complications. This study compares physical dose characteristics and anticipated risks of radiation pneumonitis (RP) among three SBRT modalities: robotic radiosurgery (RR), helical tomotherapy (HT) and volumetric modulated arc therapy (VMAT). Nine patients with central lung tumors ≤5 cm were compared. RR, HT and VMAT plans were developed per RTOG 0831. Dosimetric comparisons included target coverage, conformity index, heterogeneity index, gradient index, maximal dose at 2 cm from target (D2 cm), and dose-volume parameters for organs at risk (OARs). Efficiency endpoints included total beam-on time and monitor units. RP risk was derived from Lyman-Kutcher-Burman modeling on in-house software. The average GTV and PTV were 11.6 ± 7.86 cm3 and 36.8 ± 18.1 cm3. All techniques resulted in similar target coverage (p = 0.64) and dose conformity (p = 0.88). While RR had sharper fall-off gradient (p = 0.002) and lower D2 cm (p = 0.02), HT and VMAT produced greater homogeneity (p < 0.001) and delivery efficiency (p = 0.001). RP risk predicted from whole or contralateral lung volumes was less than 10%, but was 2-3 times higher using ipsilateral volumes. Using whole (p = 0.04, p = 0.02) or ipsilateral (p = 0.004, p = 0.0008) volumes, RR and VMAT had a lower risk of RP than HT. Using contralateral volumes, RR had the lowest RP risk (p = 0.0002, p = 0.0003 versus HT, VMAT). RR, HT and VMAT were able to provide clinically acceptable plans following the guidelines provided by RTOG 0813. All techniques provided similar coverage and conformity. RR seemed to produce a lower RP risk for a scenario of small PTV-OAR overlap and small PTV. VMAT and HT produced greater homogeneity, potentially desirable for a large PTV-OAR overlap. VMAT probably yields the lowest RP risk for a large PTV. Understanding subtle differences among these technologies may assist in situations where multiple choices of modality are available.

Interfraction Anatomical Variability Can Lead to Significantly Increased Rectal Dose for Patients Undergoing Stereotactic Body Radiotherapy for Prostate Cancer

Stereotactic body radiotherapy for prostate cancer is rapidly growing in popularity. Stereotactic body radiotherapy plans mimic those of high-dose rate brachytherapy, with tight margins and inhomogeneous dose distributions. The impact of interfraction anatomical changes on the dose received by organs at risk under these conditions has not been well documented. To estimate anatomical variation during stereotactic body radiotherapy, 10 patients were identified who received a prostate boost using robotic stereotactic body radiotherapy after completing 25 fractions of pelvic radiotherapy with daily megavoltage computed tomography. Rectal and bladder volumes were delineated on each megavoltage computed tomography, and the stereotactic body radiotherapy boost plan was registered to each megavoltage computed tomography image using a point-based rigid registration with 3 fiducial markers placed in the prostate. The volume of rectum and bladder receiving 75% of the prescription dose (V75%) was measured for each megavoltage computed tomography. The rectal V75% from the daily megavoltage computed tomographies was significantly greater than the planned V75% (median increase of 0.93 cm3, P < .001), whereas the bladder V75% on megavoltage computed tomography was not significantly changed (median decrease of −0.12 cm3, P = .57). Although daily prostate rotation was significantly correlated with bladder V75% (Spearman ρ = .21, P = .023), there was no association between rotation and rectal V75% or between prostate deformation and either rectal or bladder V75%. Planning organ-at-risk volume-based replanning techniques using either a 6-mm isotropic expansion of the plan rectal contour or a 1-cm expansion from the planning target volume in the superior and posterior directions demonstrated significantly improved rectal V75% on daily megavoltage computed tomographies compared to the original stereotactic body radiotherapy plan, without compromising plan quality. Thus, despite tight margins and full translational and rotational corrections provided by robotic stereotactic body radiotherapy, we find that interfraction anatomical variations can lead to a substantial increase in delivered rectal doses during prostate stereotactic body radiotherapy. A planning organ-at-risk volume-based approach to treatment planning may help mitigate the impact of daily organ motion and reduce the risk of rectal toxicity.

Respiration-Induced Intraorgan Deformation of the Liver.

Stereotactic body radiation therapy is a well-tolerated modality for the treatment of primary and metastatic liver lesions, and fiducials are often used as surrogates for tumor tracking during treatment. We evaluated respiratory-induced liver deformation by measuring the rigidity of the fiducial configuration during the breathing cycle. Seventeen patients, with 18 distinct treatment courses, were treated with stereotactic body radiosurgery using multiple fiducials. Liver deformation was empirically quantified by measuring the intrafiducial distances at different phases of respiration. Data points were collected at the 0%, 50%, and 100% inspiration points, and the distance between each pair of fiducials was measured at the 3 phases. The rigid body error was calculated as the maximum difference in the intrafiducial distances. Liver disease was calculated with Child-Pugh score using laboratory values within 3 months of initiation of treatment. A peripheral fiducial was defined as within 1.5 cm of the liver edge, and all other fiducials were classified as central. For 5 patients with only peripheral fiducials, the fiducial configuration had more deformation (average maximum rigid body error 7.11 mm, range: 1.89-11.35 mm) when compared to patients with both central and peripheral and central fiducials only (average maximum rigid body error 3.36 mm, range: 0.5-9.09 mm, P = .037). The largest rigid body errors (11.3 and 10.6 mm) were in 2 patients with Child-Pugh class A liver disease and multiple peripheral fiducials. The liver experiences internal deformation, and the fiducial configuration should not be assumed to act as a static structure. We observed greater deformation at the periphery than at the center of the liver. In our small data set, we were not able to identify cirrhosis, which is associated with greater rigidity of the liver, as predictive for deformation. Treatment planning based only on fiducial localization must take potential intraorgan deformation into account.

WE‐E‐108‐10: Validating a 192Ir‐Based Small Animal Irradiation Apparatus Using a 3D‐Printed Applicator: Comparison Between TG‐43, Monte Carlo and Films Dosimetry

PURPOSE Accurate assessment of dose delivered is key to early prediction of radiation-induced anatomic and physiologic changes vital in providing the most accurate patient-specific treatments. We are conducting a translational small-animal study using functional Hyperpolarized-13C-Urea with DCE-MRI to evaluate tumor perfusion changes following local targeted Ir-192 irradiation using the Leipzig applicator. The purpose of this study is to present and evaluate a novel Monte Carlo (MC) tool, which provides heterogeneous dose predictions for this specific application, and to compare the results against the TG-43 dose calculation. METHODS CT scans were obtained with a Leipzig applicator mold (fabricated using a 3D-printer to avoid metal artifact) centrally placed on top of the CyberKnife Ball Cube QA phantom . The CT density of the mold was overridden to be that of the applicator material, Tungsten. A Monte Carlo platform, ALGEBRA (ALgorithm for heterogeneous dosimetry based on GEANT4 for BRAchytherapy) was used for simulation. Dose measurements were done using Gafchromic EBT2 film placed orthogonally inside the Ball Cube exposed to Ir-192 with the Leipzig applicator in place. Simple TG-43 calculations for a free source in water was done using the Oncentra treatment planning system. RESULTS The two-dimensional planar dose distributions obtained from MC simulation showed strong agreement (within 4-5%) with dose measurements while TG-43 calculations showed differences up to 20%. Compared to TG-43, the MC Result was attenuated less at the surface because of the Leipzig air cavity, but penetrated less due to the collimation effect. CONCLUSION We have validated a new MC simulation tool using a Leipzig applicator for small animal irradiation. This tool will provide the basis for studies associating tumor response with the actual dose delivered. The tool can be further used to construct dosimetry information for clinical treatments using the Leipzig applicator as an alternative to superficial/orthovoltage radiation treatment.

An Evaluation of Robotic and Conventional IMRT for Prostate Cancer: Potential for Dose Escalation.

This study compares conventional and robotic intensity modulated radiation therapy (IMRT) plans for prostate boost treatments and provides clinical insight into the strengths and weaknesses of each. The potential for dose escalation with robotic IMRT is further investigated using the “critical volume tolerance” method proposed by Roach et al. Three clinically acceptable treatment plans were generated for 10 prostate boost patients: (1) a robotic IMRT plan using fixed cones, (2) a robotic IMRT plan using the Iris variable aperture collimator, and (3) a conventional linac based IMRT (c-IMRT) plan. Target coverage, critical structure doses, homogeneity, conformity, dose fall-off, and treatment time, were compared across plans. The average bladder and rectum V75 was 17.1%, 20.0%, and 21.4%, and 8.5%, 11.9%, and 14.1% for the Iris, fixed, and c-IMRT plans, respectively. On average the conformity index (nCI) was 1.20, 1.30, and 1.46 for the Iris, fixed, and c-IMRT plans. Differences between the Iris and the c-IMRT plans were statistically significant for the bladder V75 (P= .016), rectum V75 (P= .0013), and average nCI (P =.002). Dose to normal tissue in terms of R50 was 4.30, 5.87, and 8.37 for the Iris, fixed and c-IMRT plans, respectively, with statistically significant differences between the Iris and c-IMRT (P = .0013) and the fixed and c-IMRT (P = .001) plans. In general, the robotic IMRT plans generated using the Iris were significantly better compared to c-IMRT plans, and showed average dose gains of up to 34% for a critical rectal volume of 5%.

Image-Guided Hypofractionated Radiosurgery of Large and Complex Brain Lesions

Hypofractionated radiosurgery either through frame or image guidance has emerged as the most important area of research and development for intracranial and extracra‐ nial radiosurgery. In this chapter, we focused on discussions of three state-of-the-art platforms: Frameand Image-Guided Gamma Knife, Robotic X-Band Cykerknife, and Flattening-Filter-Free intensity-modulated S-band medical linear accelerators. Practical principles with detailed workflow and clinical implementations are presented in a systematic approach. With rapid evolvement of both hardware and software in the realm of delivering hypofractionated radiosurgery, this chapter aims to offer a reader physical clarity on judging and balancing of achieving high-precision and highquality treatments with practical examples and guidelines on intracranial applications.